Traditionally, fluids have been processed in systems that utilize stainless steel containers. These containers are sterilized after use so that they can be reused. The sterilization procedures are expensive and cumbersome as well as being ineffectual at times.
In order to provide greater flexibility in manufacturing and reduce the time needed to effect a valid regeneration of the equipment, manufacturers have begun to utilize disposable sterilized containers such as bags that are used once with a product batch and then disposed.
An example of use of these disposable bags is in a system for mixing two or more ingredients, at least one of which is liquid and the other(s) being liquid or solid, and the bag has a mixing element or the like for causing the contents to mix as uniformly as possible.
For example, in the production of vaccines, the liquids involved often contain aluminum salt as an adjuvant. The aluminum salt improves the effectiveness of the vaccine by enhancing the body's immune response. Unfortunately, the aluminum salt has particles sizes larger than 0.2 μm, and thus sterile filtering generally is not an option. As a result, it is often advantageous to minimize the number of containers into which the vaccine needs to be transferred, since each transfer represents a potential breach of sterility, and the resulting contamination can't be filtered away. Accordingly, it is advantageous to be able to mix vaccines in the same container, such as a flexible, disposable bag, that they are shipped in.
Another example is a bioreactor or fermentor in which cells are either in suspension or on microcarriers and the bag has a circulating member for circulating the liquid, gases, and in some cases the cells around the interior of the bag.
Some conventional bioreactors include a sleeve to hold a rigid metal insert that acts as a baffle for improved mixing. However, large volume bioreactors, e.g., 1000 L and 2000 L volume bioreactors, present challenges for implementing such a rigid baffle, since the increased height of these systems makes it difficult to introduce the rigid insert through the top of the bioreactor. In addition, the bottom to top mixing seen in the smaller scales becomes even more pronounced as the overall height of the bioreactor increases, even with the reduced height to width aspect ratios.
Good mixing is critical, for optimization of a bioreactor process. A well-designed mixing system provides three basic functions: creation of constant living conditions (nutrients, pH, temperature, etc.) in a homogeneous distribution; dispersion of gas for supplying O2 and extracting CO2; and optimization of heat transfer. Providing acceptable mixing, without imparting damaging shear effects, becomes more challenging as the scale of the bioreactor container increases. Some commercial bioreactor platforms include a single bottom mounted impeller. The formation of a vortex, with stagnant zones, is often associated with this single agitator. A baffle can be added to suppress vortex formation and provide for movement of the fluid into a preferred flow pattern of axial and radial flow. The inclusion of a well-designed baffle will allow for better mixing efficiency without the added high shear risk associated with multiple impellers and/or high impeller speeds.
It therefore would be desirable to provide a disposable or single use container for fluids with an improved baffle system to achieve homogeneous mixing necessary for optimal cell culture growth performance in bioreactors.